Schwann cell-secreted PGE2 promotes sensory neuron excitability during development [scRNAseq_Dataset2]

Electrical excitability—the ability to fire and propagate action potentials—is a signature feature of neurons. How neurons become excitable during development and whether excitability is an intrinsic property of neurons or requires signaling from glial cells remain unclear. Here, we demonstrate that Schwann cells, the most abundant glia in the peripheral nervous system, promote somatosensory neuron excitability during development. We find that Schwann cells secrete prostaglandin E2, which is necessary and sufficient to induce developing somatosensory neurons to express normal levels of genes required for neuronal function, including voltage gated sodium channels, and to fire action potential trains. In this scRNAseq study, we found that inactivating PGE2 synthesis in Schwann cells, in vivo, impaired somatosensory neuron maturation, with the most dramatic effects on nociceptor and proprioceptor somatosensory neuron subtypes. Overall design: DRG ganglia from all axial levels were dissected from Ptges3-Flox and Ptges3-cKO mice at P4 stage and DRG neurons were analyzed using scRNASeq. Actinomycin D was used during dissection steps to block new transcription during dissection